Time of pulsatile ghrelin administration determines effect on sleep

Ghrelin is a peptide hormone acting at the growth hormone (GH) secretagogue (GHS) receptor. It was isolated from stomach and CNS of rats and humans. The substance has been shown to participate in the regulation of endocrine activity, energy balance and sleep. Since the sleeping period is a time of considerable activity in various endocrine systems, we were interested in the sleep-related pattern after ghrelin administration and its interaction with sleep EEG and with other hormones. Ghrelin and GH releasing hormone (GHRH) both stimulate GH secretion and slow wave sleep (SWS), whereas ghrelin increases, and GHRH decreases cortisol in males. However, GHRH's effect on sleep and cortisol was abolished, on GH mitigated, when administered in the early morning, possibly due to counteracting corticotropin releasing hormone (CRH).

To investigate ghrelin's influence on sleep, GH and cortisol when administered in the early morning. Nocturnal (2000–1000h) GH and cortisol patterns and polysomnography (2300–1000h) were examined simultanously in 12 healthy males (25.3±3.2 years) twice, receiving 50µg ghrelin or placebo at 0400, 0500, 0600, and 0700h, in this single-blind, randomized, cross-over study. The first ghrelin bolus caused the strongest (38.7±6.5 ng/ml, placebo: 0.4±1.1 ng/ml), second and third smaller, the fourth no GH peak. GH levels remained significantly (p<0.05) higher from 0420–0740h in the ghrelin condition. Comparably, the first ghrelin bolus caused the strongest cortisol response (156.0±12.6 ng/ml; placebo: 78.0±10.5 ng/ml). Cortisol was significantly higher from 0440–0540 and at 0720h and decreased thereafter to significantly lower levels (0820–0840h). Sleep variables did not differ in both conditions.

In contrast to GHRH, ghrelin's stimulatory effects were apparently not counteracted (GH), and enhanced (cortisol) respectively by high CRH in the second half of night. Ghrelin did not affect sleep, consistent with the hypothesis that ghrelin's SWS promoting effect is mediated by GHRH.